ABSTRACT

BACKGROUND: About 10% of people in the United States develop at least 1 symptomatic kidney stone during their lives. The recurrence rate after 10 years is at least 50%. Many physicians recommend a low-calcium diet in patients with calcium oxalate stones to prevent recurrence. Recent studies suggest that a low-calcium diet may not be effective and that intake of animal protein and salt may influence renal calcium excretion. This study compares the traditional low-calcium diet with a diet that is low in animal protein and salt.

POPULATION STUDIED: This study enrolled 120 men with idiopathic hypercalciuria (urinary calcium excretion of more than 300 mg per day on an unrestricted diet) who had been referred to a nephrology clinic in Parma, Italy, and who had had at least 2 episodes of symptomatic renal stones. Reasons for exclusion included previous visits to any “stone disease center” and conditions associated with calcium stones, such as hyperparathyroidism or inflammatory bowel disease.

STUDY DESIGN AND VALIDITY: The investigators randomly assigned subjects, using concealed allocation, to 1 of 2 diets in this randomized controlled study. The low-calcium diet limited calcium intake to about 400 mg per day. The other diet, which included about 1200 mg per day of calcium, limited sodium chloride to about 3000 mg and animal protein to 93 g (15% of total calories). Both groups were advised to limit intake of high-oxalate foods and encouraged to drink 2 liters of water per day in cold weather and 3 liters in warm weather. Subjects were allowed moderate consumption of beer, wine, coffee, and sodas. (Detailed dietary instructions are available to New England Journal of Medicine subscribers in the supplement to the publication at www.nejm.org.) The study followed the patients for 5 years or until they developed clinical or radiologic evidence of a renal stone. Annual x-ray and ultrasound studies identified asymptomatic stone recurrences.

OUTCOMES MEASURED: The primary outcome was the time to development of the first recurrence of a renal stone, whether or not it was clinically evident. Other outcomes included changes in calcium and oxalate excretion and calcium oxalate saturation in the urine.

RESULTS: After 5 years, the low-protein, low-sodium diet led to fewer recurrences (20% compared with 38% in the low-calcium group, relative risk 0.49, number needed to treat with diet for 5 years = 5.5). The risk of recurrence in the low-calcium group was similar to the 35% to 40% expected in the absence of any intervention. The disease-oriented changes in urine characteristics were predictable: urinary calcium decreased in both groups, but oxalate secretion increased in the low-calcium group, causing greater calcium oxalate saturation.

ABSTRACT

BACKGROUND: About 10% of people in the United States develop at least 1 symptomatic kidney stone during their lives. The recurrence rate after 10 years is at least 50%. Many physicians recommend a low-calcium diet in patients with calcium oxalate stones to prevent recurrence. Recent studies suggest that a low-calcium diet may not be effective and that intake of animal protein and salt may influence renal calcium excretion. This study compares the traditional low-calcium diet with a diet that is low in animal protein and salt.

POPULATION STUDIED: This study enrolled 120 men with idiopathic hypercalciuria (urinary calcium excretion of more than 300 mg per day on an unrestricted diet) who had been referred to a nephrology clinic in Parma, Italy, and who had had at least 2 episodes of symptomatic renal stones. Reasons for exclusion included previous visits to any “stone disease center” and conditions associated with calcium stones, such as hyperparathyroidism or inflammatory bowel disease.

STUDY DESIGN AND VALIDITY: The investigators randomly assigned subjects, using concealed allocation, to 1 of 2 diets in this randomized controlled study. The low-calcium diet limited calcium intake to about 400 mg per day. The other diet, which included about 1200 mg per day of calcium, limited sodium chloride to about 3000 mg and animal protein to 93 g (15% of total calories). Both groups were advised to limit intake of high-oxalate foods and encouraged to drink 2 liters of water per day in cold weather and 3 liters in warm weather. Subjects were allowed moderate consumption of beer, wine, coffee, and sodas. (Detailed dietary instructions are available to New England Journal of Medicine subscribers in the supplement to the publication at www.nejm.org.) The study followed the patients for 5 years or until they developed clinical or radiologic evidence of a renal stone. Annual x-ray and ultrasound studies identified asymptomatic stone recurrences.

OUTCOMES MEASURED: The primary outcome was the time to development of the first recurrence of a renal stone, whether or not it was clinically evident. Other outcomes included changes in calcium and oxalate excretion and calcium oxalate saturation in the urine.

RESULTS: After 5 years, the low-protein, low-sodium diet led to fewer recurrences (20% compared with 38% in the low-calcium group, relative risk 0.49, number needed to treat with diet for 5 years = 5.5). The risk of recurrence in the low-calcium group was similar to the 35% to 40% expected in the absence of any intervention. The disease-oriented changes in urine characteristics were predictable: urinary calcium decreased in both groups, but oxalate secretion increased in the low-calcium group, causing greater calcium oxalate saturation.

ABSTRACT

BACKGROUND: About 10% of people in the United States develop at least 1 symptomatic kidney stone during their lives. The recurrence rate after 10 years is at least 50%. Many physicians recommend a low-calcium diet in patients with calcium oxalate stones to prevent recurrence. Recent studies suggest that a low-calcium diet may not be effective and that intake of animal protein and salt may influence renal calcium excretion. This study compares the traditional low-calcium diet with a diet that is low in animal protein and salt.

POPULATION STUDIED: This study enrolled 120 men with idiopathic hypercalciuria (urinary calcium excretion of more than 300 mg per day on an unrestricted diet) who had been referred to a nephrology clinic in Parma, Italy, and who had had at least 2 episodes of symptomatic renal stones. Reasons for exclusion included previous visits to any “stone disease center” and conditions associated with calcium stones, such as hyperparathyroidism or inflammatory bowel disease.

STUDY DESIGN AND VALIDITY: The investigators randomly assigned subjects, using concealed allocation, to 1 of 2 diets in this randomized controlled study. The low-calcium diet limited calcium intake to about 400 mg per day. The other diet, which included about 1200 mg per day of calcium, limited sodium chloride to about 3000 mg and animal protein to 93 g (15% of total calories). Both groups were advised to limit intake of high-oxalate foods and encouraged to drink 2 liters of water per day in cold weather and 3 liters in warm weather. Subjects were allowed moderate consumption of beer, wine, coffee, and sodas. (Detailed dietary instructions are available to New England Journal of Medicine subscribers in the supplement to the publication at www.nejm.org.) The study followed the patients for 5 years or until they developed clinical or radiologic evidence of a renal stone. Annual x-ray and ultrasound studies identified asymptomatic stone recurrences.

OUTCOMES MEASURED: The primary outcome was the time to development of the first recurrence of a renal stone, whether or not it was clinically evident. Other outcomes included changes in calcium and oxalate excretion and calcium oxalate saturation in the urine.

RESULTS: After 5 years, the low-protein, low-sodium diet led to fewer recurrences (20% compared with 38% in the low-calcium group, relative risk 0.49, number needed to treat with diet for 5 years = 5.5). The risk of recurrence in the low-calcium group was similar to the 35% to 40% expected in the absence of any intervention. The disease-oriented changes in urine characteristics were predictable: urinary calcium decreased in both groups, but oxalate secretion increased in the low-calcium group, causing greater calcium oxalate saturation.

Making a quick diagnosis in a hyperactive, inattentive child is often difficult. The National Institutes of Health concluded in a consensus statement that no independent diagnostic test for attention-deficit/hyperactivity disorder (ADHD) exists.¹ Furthermore, the American Academy of Child & Adolescent Psychiatry (AACAP) issued a treatment guideline classifying ADHD as a clinical diagnosis.

With the time constraints imposed by managed care organizations, questioning and history gathering must be precisely aimed to elicit specific information. Over the years, I have identified the following 5 red flags that help distinguish ADHD from mood problems,² anxiety, psychosis, obsessions, and other psychiatric disorders.

1. Moodiness is not part of ADHD. The DSM-IV criteria for ADHD do not include elevated mood. “Mood swings,” persistent clowning, or angry affect should prompt further questioning about similar features in relatives. Frequently we hear that “his father was never diagnosed with anything, but he was the class clown.”
2. ADHD is not an intermittent condition. By asking if the child has “good days and bad days,” we can obtain valuable information. ADHD has a biological basis and is present every day, like Parkinson’s disease or diabetes. Obviously, some days can be more challenging than others, but if a parent says, “Some days she is a perfect child,” the possibility of ADHD is small.
3. Symptoms are not present in kindergarten. The child with ADHD begins to show signs of this condition very early in life; parents are frequently informed of problems by preschool and kindergarten teachers. The usual complaints are inability to stay with a task and disrupting the class. Start of these symptoms as late as first or second grade is a red flag to question the ADHD diagnosis.
4. More than one diagnosis probably means “none of the above.” When a child has been diagnosed with conduct disorder (CD) and/or oppositional-defiant disorder (ODD) along with ADHD, chances are that we are missing the real diagnosis. I have seen cases of social anxiety disorder that had been diagnosed as ADHD/ODD because the child was inattentive secondary to nervousness. Incidentally, DSM-IV does not allow the diagnosis of ODD in the presence of CD.
5. Worsening of symptoms is not an expected outcome of stimulant medications for ADHD. Lack of response to psychostimulants or only mild improvement may occur in ADHD. Frequently, however, we see children with histories of getting worse after starting medication for presumed ADHD.

Making a quick diagnosis in a hyperactive, inattentive child is often difficult. The National Institutes of Health concluded in a consensus statement that no independent diagnostic test for attention-deficit/hyperactivity disorder (ADHD) exists.¹ Furthermore, the American Academy of Child & Adolescent Psychiatry (AACAP) issued a treatment guideline classifying ADHD as a clinical diagnosis.

With the time constraints imposed by managed care organizations, questioning and history gathering must be precisely aimed to elicit specific information. Over the years, I have identified the following 5 red flags that help distinguish ADHD from mood problems,² anxiety, psychosis, obsessions, and other psychiatric disorders.

1. Moodiness is not part of ADHD. The DSM-IV criteria for ADHD do not include elevated mood. “Mood swings,” persistent clowning, or angry affect should prompt further questioning about similar features in relatives. Frequently we hear that “his father was never diagnosed with anything, but he was the class clown.”
2. ADHD is not an intermittent condition. By asking if the child has “good days and bad days,” we can obtain valuable information. ADHD has a biological basis and is present every day, like Parkinson’s disease or diabetes. Obviously, some days can be more challenging than others, but if a parent says, “Some days she is a perfect child,” the possibility of ADHD is small.
3. Symptoms are not present in kindergarten. The child with ADHD begins to show signs of this condition very early in life; parents are frequently informed of problems by preschool and kindergarten teachers. The usual complaints are inability to stay with a task and disrupting the class. Start of these symptoms as late as first or second grade is a red flag to question the ADHD diagnosis.
4. More than one diagnosis probably means “none of the above.” When a child has been diagnosed with conduct disorder (CD) and/or oppositional-defiant disorder (ODD) along with ADHD, chances are that we are missing the real diagnosis. I have seen cases of social anxiety disorder that had been diagnosed as ADHD/ODD because the child was inattentive secondary to nervousness. Incidentally, DSM-IV does not allow the diagnosis of ODD in the presence of CD.
5. Worsening of symptoms is not an expected outcome of stimulant medications for ADHD. Lack of response to psychostimulants or only mild improvement may occur in ADHD. Frequently, however, we see children with histories of getting worse after starting medication for presumed ADHD.

Making a quick diagnosis in a hyperactive, inattentive child is often difficult. The National Institutes of Health concluded in a consensus statement that no independent diagnostic test for attention-deficit/hyperactivity disorder (ADHD) exists.¹ Furthermore, the American Academy of Child & Adolescent Psychiatry (AACAP) issued a treatment guideline classifying ADHD as a clinical diagnosis.

With the time constraints imposed by managed care organizations, questioning and history gathering must be precisely aimed to elicit specific information. Over the years, I have identified the following 5 red flags that help distinguish ADHD from mood problems,² anxiety, psychosis, obsessions, and other psychiatric disorders.

1. Moodiness is not part of ADHD. The DSM-IV criteria for ADHD do not include elevated mood. “Mood swings,” persistent clowning, or angry affect should prompt further questioning about similar features in relatives. Frequently we hear that “his father was never diagnosed with anything, but he was the class clown.”
2. ADHD is not an intermittent condition. By asking if the child has “good days and bad days,” we can obtain valuable information. ADHD has a biological basis and is present every day, like Parkinson’s disease or diabetes. Obviously, some days can be more challenging than others, but if a parent says, “Some days she is a perfect child,” the possibility of ADHD is small.
3. Symptoms are not present in kindergarten. The child with ADHD begins to show signs of this condition very early in life; parents are frequently informed of problems by preschool and kindergarten teachers. The usual complaints are inability to stay with a task and disrupting the class. Start of these symptoms as late as first or second grade is a red flag to question the ADHD diagnosis.
4. More than one diagnosis probably means “none of the above.” When a child has been diagnosed with conduct disorder (CD) and/or oppositional-defiant disorder (ODD) along with ADHD, chances are that we are missing the real diagnosis. I have seen cases of social anxiety disorder that had been diagnosed as ADHD/ODD because the child was inattentive secondary to nervousness. Incidentally, DSM-IV does not allow the diagnosis of ODD in the presence of CD.
5. Worsening of symptoms is not an expected outcome of stimulant medications for ADHD. Lack of response to psychostimulants or only mild improvement may occur in ADHD. Frequently, however, we see children with histories of getting worse after starting medication for presumed ADHD.

ABSTRACT

BACKGROUND: Symptoms resulting from early response to allergen exposure are histamine mediated, last a few minutes, and often cue patients to take medication. Hours later, the late response begins and typically leads to symptoms of congestion. The late-phase response is not histamine mediated; other studies have shown intranasal corticosteroids to inhibit the response. The researchers tested the hypothesis that intranasal steroids may be as beneficial as or superior to antihistamines for as-needed use because of their effect on the late response to environmental allergens.

POPULATION STUDIED: The 88 subjects, aged 18 to 48 years, had fall seasonal rhinitis for at least 2 ragweed seasons before enrollment and had a positive puncture skin test to ragweed antigen extract. The population was 52% male, 60% white and in general good health. Patients were excluded for nasal polyps, displaced septum, perennial rhinitis, and signs or symptoms of renal, hepatic, or cardiovascular disease. Patients were also excluded if they had received immunotherapy within 2 years before enrollment or had taken topical or systemic steroids, antihistamines, decongestants, or cromolyn sodium within 2 weeks before enrollment.

STUDY DESIGN AND VALIDITY: This is a randomized unblinded study. Patients were enrolled before or during the early part of the ragweed season. They were randomized to receive 100 μg/day fluticasone propionate per nostril or 10 mg loratadine once daily as needed for 4 weeks. Nasal lavage for eosinophil count and eosinophil cationic protein (ECP) and completion of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ, a validated instrument) were performed initially, at 2 weeks, and at 4 weeks. Patients were instructed to record medication usage and symptom severity in a diary twice daily. Itchy eyes and 3 symptoms for each nostril (rhinorrhea, nasal congestion, and sneezing) were rated on a scale of 0 to 3, ranging from 0 = no symptoms to 3 = severe symptoms.

OUTCOMES MEASURED: The RQLQ score was the primary outcome. The symptom diary scores were evaluated by symptom; a total symptom score was calculated. Other outcomes included nasal lavage eosinophil count and ECP levels.

RESULTS: Patients used medication an average of 17 of 28 days in the fluticasone group, similar to the average of 18 of 28 days in the loratadine group. The RQLQ scores were similar in the 2 groups initially. Significant improvement in the fluticasone group over the loratadine group was seen at the second and third visits in the overall score and activity, sleep, practical, and nasal domains of the RQLQ (P < .05). Symptom diaries showed a median score of 7.0 out of 21 for the loratadine-treated group and 4.0 out of 21 for the steroid-treated group (P = .005). Eosinophil count and ECP showed significant decreases in the steroid group.

ABSTRACT

BACKGROUND: Symptoms resulting from early response to allergen exposure are histamine mediated, last a few minutes, and often cue patients to take medication. Hours later, the late response begins and typically leads to symptoms of congestion. The late-phase response is not histamine mediated; other studies have shown intranasal corticosteroids to inhibit the response. The researchers tested the hypothesis that intranasal steroids may be as beneficial as or superior to antihistamines for as-needed use because of their effect on the late response to environmental allergens.

POPULATION STUDIED: The 88 subjects, aged 18 to 48 years, had fall seasonal rhinitis for at least 2 ragweed seasons before enrollment and had a positive puncture skin test to ragweed antigen extract. The population was 52% male, 60% white and in general good health. Patients were excluded for nasal polyps, displaced septum, perennial rhinitis, and signs or symptoms of renal, hepatic, or cardiovascular disease. Patients were also excluded if they had received immunotherapy within 2 years before enrollment or had taken topical or systemic steroids, antihistamines, decongestants, or cromolyn sodium within 2 weeks before enrollment.

STUDY DESIGN AND VALIDITY: This is a randomized unblinded study. Patients were enrolled before or during the early part of the ragweed season. They were randomized to receive 100 μg/day fluticasone propionate per nostril or 10 mg loratadine once daily as needed for 4 weeks. Nasal lavage for eosinophil count and eosinophil cationic protein (ECP) and completion of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ, a validated instrument) were performed initially, at 2 weeks, and at 4 weeks. Patients were instructed to record medication usage and symptom severity in a diary twice daily. Itchy eyes and 3 symptoms for each nostril (rhinorrhea, nasal congestion, and sneezing) were rated on a scale of 0 to 3, ranging from 0 = no symptoms to 3 = severe symptoms.

OUTCOMES MEASURED: The RQLQ score was the primary outcome. The symptom diary scores were evaluated by symptom; a total symptom score was calculated. Other outcomes included nasal lavage eosinophil count and ECP levels.

RESULTS: Patients used medication an average of 17 of 28 days in the fluticasone group, similar to the average of 18 of 28 days in the loratadine group. The RQLQ scores were similar in the 2 groups initially. Significant improvement in the fluticasone group over the loratadine group was seen at the second and third visits in the overall score and activity, sleep, practical, and nasal domains of the RQLQ (P < .05). Symptom diaries showed a median score of 7.0 out of 21 for the loratadine-treated group and 4.0 out of 21 for the steroid-treated group (P = .005). Eosinophil count and ECP showed significant decreases in the steroid group.

ABSTRACT

BACKGROUND: Symptoms resulting from early response to allergen exposure are histamine mediated, last a few minutes, and often cue patients to take medication. Hours later, the late response begins and typically leads to symptoms of congestion. The late-phase response is not histamine mediated; other studies have shown intranasal corticosteroids to inhibit the response. The researchers tested the hypothesis that intranasal steroids may be as beneficial as or superior to antihistamines for as-needed use because of their effect on the late response to environmental allergens.

POPULATION STUDIED: The 88 subjects, aged 18 to 48 years, had fall seasonal rhinitis for at least 2 ragweed seasons before enrollment and had a positive puncture skin test to ragweed antigen extract. The population was 52% male, 60% white and in general good health. Patients were excluded for nasal polyps, displaced septum, perennial rhinitis, and signs or symptoms of renal, hepatic, or cardiovascular disease. Patients were also excluded if they had received immunotherapy within 2 years before enrollment or had taken topical or systemic steroids, antihistamines, decongestants, or cromolyn sodium within 2 weeks before enrollment.

STUDY DESIGN AND VALIDITY: This is a randomized unblinded study. Patients were enrolled before or during the early part of the ragweed season. They were randomized to receive 100 μg/day fluticasone propionate per nostril or 10 mg loratadine once daily as needed for 4 weeks. Nasal lavage for eosinophil count and eosinophil cationic protein (ECP) and completion of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ, a validated instrument) were performed initially, at 2 weeks, and at 4 weeks. Patients were instructed to record medication usage and symptom severity in a diary twice daily. Itchy eyes and 3 symptoms for each nostril (rhinorrhea, nasal congestion, and sneezing) were rated on a scale of 0 to 3, ranging from 0 = no symptoms to 3 = severe symptoms.

OUTCOMES MEASURED: The RQLQ score was the primary outcome. The symptom diary scores were evaluated by symptom; a total symptom score was calculated. Other outcomes included nasal lavage eosinophil count and ECP levels.

RESULTS: Patients used medication an average of 17 of 28 days in the fluticasone group, similar to the average of 18 of 28 days in the loratadine group. The RQLQ scores were similar in the 2 groups initially. Significant improvement in the fluticasone group over the loratadine group was seen at the second and third visits in the overall score and activity, sleep, practical, and nasal domains of the RQLQ (P < .05). Symptom diaries showed a median score of 7.0 out of 21 for the loratadine-treated group and 4.0 out of 21 for the steroid-treated group (P = .005). Eosinophil count and ECP showed significant decreases in the steroid group.

ABSTRACT

BACKGROUND: Adding 2 to 3 doses of ipratropium bromide (Atrovent) to conventional therapy with inhaled β-agonists and systemic corticosteroids improves lung function and decreases hospital admissions when given in the emergency department (ED). This study evaluated whether ipratropium bromide administration improves outcomes in children who require subsequent hospitalization.

POPULATION STUDIED: The authors enrolled 80 children aged 1 to 18 years with a history of asthma admitted to the pediatric inpatient unit of a tertiary-care urban hospital. Children had to have moderate to severe symptoms upon admission, defined as requiring inhaled β₂-agonists at least every 2 hours, having a forced expiratory volume in 1 second (FEV₁) of 25% to 80% of predicted, or having a clinical asthma score of 3 to 9 out of a possible 10. The clinical asthma score is a total of 5 items—respiratory rate, wheezing, inspiratory–expiratory ratio, retracting, and observed dyspnea—scored on a 3-point scale. Excluded patients had coexisting cardiac, neurologic, immunosuppressive, or other chronic pulmonary disease, hypersensitivity to the study drugs, or known ocular abnormalities. Children were excluded if their asthma score was 10, if they needed airway intervention, or if more than 12 hours had elapsed between the first nebulizer treatment and admission.

STUDY DESIGN AND VALIDITY: This was a double-blind randomized controlled trial. Study patients received frequent nebulized albuterol at 0.15 mg/kg as well as either IV hydrocortisone at 4 to 6 mg/kg every 6 hours or oral prednisone 1 mg/kg once daily. Attending physicians determined nebulizer treatment frequency, ranging from 30 minutes to 4 hours. Subjects were randomized to receive either ipratropium bromide or normal saline, matched to the albuterol dosing interval. Participants were stratified by age (less than 5 years vs 5 years or more) and by the number of ipratropium bromide doses they received in the ED (3 or less vs more than 3). Investigators used an intention-to-treat analysis and allocation was concealed.

OUTCOMES MEASURED: The primary outcome was the clinical asthma score, measured at baseline and every 6 hours until discharge. The clinical score is reproducible, valid, and predictive. Secondary outcomes included oxygen saturation, FEV₁, length of stay, time to a 4-hour albuterol dosing interval, and readmission to the hospital or ED within 72 hours of discharge.

RESULTS: Of the 212 patients assessed for the trial, only 99 were eligible. Of these, 84 parents consented to enroll their children (4 children were later determined not to meet inclusion criteria and were excluded). The ipratropium and placebo groups were essentially the same. There was no difference in the asthma score between treatment and control groups in 3 of the 4 subgroups. In one subgroup—those who had fewer than 3 doses of ipratropium bromide in the ED—ipratropium provided a slight benefit. The difference in change in scores was 0.5 on the clinical asthma score, a statistically but not clinically important change. There were no differences in the secondary outcomes. The average heart rate was 6 to 10 beats per minute greater in the ipratropium group. The authors noted no transient anisocoria, a potential adverse effect of ipratropium bromide in children.

ABSTRACT

BACKGROUND: Adding 2 to 3 doses of ipratropium bromide (Atrovent) to conventional therapy with inhaled β-agonists and systemic corticosteroids improves lung function and decreases hospital admissions when given in the emergency department (ED). This study evaluated whether ipratropium bromide administration improves outcomes in children who require subsequent hospitalization.

POPULATION STUDIED: The authors enrolled 80 children aged 1 to 18 years with a history of asthma admitted to the pediatric inpatient unit of a tertiary-care urban hospital. Children had to have moderate to severe symptoms upon admission, defined as requiring inhaled β₂-agonists at least every 2 hours, having a forced expiratory volume in 1 second (FEV₁) of 25% to 80% of predicted, or having a clinical asthma score of 3 to 9 out of a possible 10. The clinical asthma score is a total of 5 items—respiratory rate, wheezing, inspiratory–expiratory ratio, retracting, and observed dyspnea—scored on a 3-point scale. Excluded patients had coexisting cardiac, neurologic, immunosuppressive, or other chronic pulmonary disease, hypersensitivity to the study drugs, or known ocular abnormalities. Children were excluded if their asthma score was 10, if they needed airway intervention, or if more than 12 hours had elapsed between the first nebulizer treatment and admission.

STUDY DESIGN AND VALIDITY: This was a double-blind randomized controlled trial. Study patients received frequent nebulized albuterol at 0.15 mg/kg as well as either IV hydrocortisone at 4 to 6 mg/kg every 6 hours or oral prednisone 1 mg/kg once daily. Attending physicians determined nebulizer treatment frequency, ranging from 30 minutes to 4 hours. Subjects were randomized to receive either ipratropium bromide or normal saline, matched to the albuterol dosing interval. Participants were stratified by age (less than 5 years vs 5 years or more) and by the number of ipratropium bromide doses they received in the ED (3 or less vs more than 3). Investigators used an intention-to-treat analysis and allocation was concealed.

OUTCOMES MEASURED: The primary outcome was the clinical asthma score, measured at baseline and every 6 hours until discharge. The clinical score is reproducible, valid, and predictive. Secondary outcomes included oxygen saturation, FEV₁, length of stay, time to a 4-hour albuterol dosing interval, and readmission to the hospital or ED within 72 hours of discharge.

RESULTS: Of the 212 patients assessed for the trial, only 99 were eligible. Of these, 84 parents consented to enroll their children (4 children were later determined not to meet inclusion criteria and were excluded). The ipratropium and placebo groups were essentially the same. There was no difference in the asthma score between treatment and control groups in 3 of the 4 subgroups. In one subgroup—those who had fewer than 3 doses of ipratropium bromide in the ED—ipratropium provided a slight benefit. The difference in change in scores was 0.5 on the clinical asthma score, a statistically but not clinically important change. There were no differences in the secondary outcomes. The average heart rate was 6 to 10 beats per minute greater in the ipratropium group. The authors noted no transient anisocoria, a potential adverse effect of ipratropium bromide in children.

ABSTRACT

BACKGROUND: Adding 2 to 3 doses of ipratropium bromide (Atrovent) to conventional therapy with inhaled β-agonists and systemic corticosteroids improves lung function and decreases hospital admissions when given in the emergency department (ED). This study evaluated whether ipratropium bromide administration improves outcomes in children who require subsequent hospitalization.

POPULATION STUDIED: The authors enrolled 80 children aged 1 to 18 years with a history of asthma admitted to the pediatric inpatient unit of a tertiary-care urban hospital. Children had to have moderate to severe symptoms upon admission, defined as requiring inhaled β₂-agonists at least every 2 hours, having a forced expiratory volume in 1 second (FEV₁) of 25% to 80% of predicted, or having a clinical asthma score of 3 to 9 out of a possible 10. The clinical asthma score is a total of 5 items—respiratory rate, wheezing, inspiratory–expiratory ratio, retracting, and observed dyspnea—scored on a 3-point scale. Excluded patients had coexisting cardiac, neurologic, immunosuppressive, or other chronic pulmonary disease, hypersensitivity to the study drugs, or known ocular abnormalities. Children were excluded if their asthma score was 10, if they needed airway intervention, or if more than 12 hours had elapsed between the first nebulizer treatment and admission.

STUDY DESIGN AND VALIDITY: This was a double-blind randomized controlled trial. Study patients received frequent nebulized albuterol at 0.15 mg/kg as well as either IV hydrocortisone at 4 to 6 mg/kg every 6 hours or oral prednisone 1 mg/kg once daily. Attending physicians determined nebulizer treatment frequency, ranging from 30 minutes to 4 hours. Subjects were randomized to receive either ipratropium bromide or normal saline, matched to the albuterol dosing interval. Participants were stratified by age (less than 5 years vs 5 years or more) and by the number of ipratropium bromide doses they received in the ED (3 or less vs more than 3). Investigators used an intention-to-treat analysis and allocation was concealed.

OUTCOMES MEASURED: The primary outcome was the clinical asthma score, measured at baseline and every 6 hours until discharge. The clinical score is reproducible, valid, and predictive. Secondary outcomes included oxygen saturation, FEV₁, length of stay, time to a 4-hour albuterol dosing interval, and readmission to the hospital or ED within 72 hours of discharge.

RESULTS: Of the 212 patients assessed for the trial, only 99 were eligible. Of these, 84 parents consented to enroll their children (4 children were later determined not to meet inclusion criteria and were excluded). The ipratropium and placebo groups were essentially the same. There was no difference in the asthma score between treatment and control groups in 3 of the 4 subgroups. In one subgroup—those who had fewer than 3 doses of ipratropium bromide in the ED—ipratropium provided a slight benefit. The difference in change in scores was 0.5 on the clinical asthma score, a statistically but not clinically important change. There were no differences in the secondary outcomes. The average heart rate was 6 to 10 beats per minute greater in the ipratropium group. The authors noted no transient anisocoria, a potential adverse effect of ipratropium bromide in children.